A group of thirty immunotoxicology experts from the U.S. and E.U. representing government, industry, and academia met in May 2003, in Washington, D.C., to reach consensus regarding the most appropriate methods to assess developmental immunotoxicology (DIT) for hazard identification, including under what conditions such testing might be required. The… (More)

In recent years, there has been increasing regulatory pressure to protect the health of children, with the basic tenet being that children differ significantly from adults in their biological or physiological responses to chemical exposures. In a regulatory context, this has been translated to mean a requirement for an additional 10-fold safety factor for… (More)

Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that… (More)

The evolution of the subdiscipline of developmental immunotoxicology (DIT) as it exists today has been shaped by significant regulatory pressures as well as key scientific advances. This review considers the role played by legislation to protect children's health, and on the emergence of immunotoxcity and developmental immunotoxicity guidelines, as well as… (More)

Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with a wide range of commercial applications. The present study was designed to investigate the effects of D5 on the expression and activity of selected rat hepatic phase I and phase II metabolizing enzymes. Female Fischer-344 rats were exposed to 160 ppm D5 vapors (6 h/day, 7 days/week, for 28 days) by… (More)

There has been an explosion of technology-enabled scientific insight into the basic biology of the causes of adverse events. This has been driven, in part, by the development of the various "omics" tools (e.g., genomics, proteomics, and metabolomics) and associated bioinformatics platforms. Meanwhile, for decades, changes in preclinical testing protocols… (More)

Dexamethasone was given in 2 oral dosing regimens with repeat dose oral administration of the gamma secretase inhibitor (GSI), PF-03084014, in Sprague-Dawley (SD) rats in order to evaluate the effects of coadministration of dexamethasone on GSI-induced goblet cell hyperplasia (GCH) in the intestinal tract. Safety end points were evaluated in 1 week and 1… (More)

D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to evaluate the subchronic toxicity of D5 following a 3-month nose-only inhalation exposure. In addition, animals from both sexes of the control and high dose groups were allowed a 4-week recovery period to observe… (More)